Pseudoxanthoma elasticum (PXE) is a hereditary disease characterized by abnormal calcium-polyanion complexes within affected dermal, occular and vascular elastic fibers. Cultured medium from fibroblasts from dermis of patients with PXE have increased proteolytic activity that can degrade 35S-labelled proteoglycans. The proposed research will further evaluate the "PXE protease" and try to determine its role in the pathogenesis of PXE. An effective assay will be developed and the protease will be purified. The enzymatic characteristics of the pure protease will be determined. An antibody will be developed to the protease and used to determine the immunohistochemical localization of the antigen in PXE dermis. An in vitro culture system is proposed that may provide a method of determining the role of the protease and other factors in the pathogenesis of PXE. Preliminary studies have demonstrated increased levels of gamma-carboxyglutamic acid (Gla) in PXE dermis. Since Gla has been demonstrated in both protease and non protease-calcium binding proteins, it is proposed to study the Gla containing proteins in PXE dermis and determine their role in the abnormal mineralization. This study will clarify the role of the protease activity in this disease and may provide information on the relationship of proteases to other connective tissue diseases. Furthermore, information derived from this study may be important in establishing an effective treatment for the disease.